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Background: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment. Results: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin). Conclusion: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a kind of kidney disease with a high mortality rate, and is predominantly associated with abundant endogenous reactive oxygen/nitrogen species (RONS). However, there are no universal clinical treatment options currently. Development of antioxidants with high kidney enrichment is highly desired to prevent AKI. As a promising new artificial enzyme, nanozymes have attracted extensive attention over the past decade because of their commendable advantages over natural and traditional artificial enzymes. In this study, we reported ultrasmall polyvinylpyrrolidone-coated iridium nanoparticles (denoted as Ir NPs-PVP, 1.5 nm) as multi-enzyme mimetic to scavenge a variety of RONS, offering an efficient RONS-induced cellular protection. Meanwhile, computed tomography and inductively coupled plasma mass spectrometry demonstrated preferential renal uptake of Ir NPs-PVP following intravenous administration, leading to alleviate clinical symptoms in mice subjected to rhabdomyolysis- or cis-platinum-induced AKI. Impressively, ultrasmall Ir NPs-PVP exhibit relatively low systemic side effects in vivo due to rapid renal clearance via urine. Our work presents the clinically translatable potential of ultrasmall nanozymes for AKI management. [Display omitted] [ABSTRACT FROM AUTHOR]